DOCSLIB.ORG

Facioscapulohumeral Muscular Dystrophy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Facioscapulohumeral Muscular Dystrophy Lab Management Guidelines V1.0.2020 Genetic Testing for Facioscapulohumeral Muscular Dystrophy MOL.TS.290.A v1.0.2020 Introduction Facioscapulohumeral Muscular Dystrophy testing is addressed by this guideline. Procedures addressed The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements. Procedure addressed by this guideline Procedure code D4Z4 region (FSHMD1A) deletion 81404 analysis D4Z4 region (FSHMD1A) methylation 81479 analysis FSHMD1 characterization of 4qA/4qB 81404 haplotypes SMCHD1 sequencing 81479 SMCHD1 deletion/duplication analysis 81479 What is Facioscapulohumeral Muscular Dystrophy Definition Facioscapulohumeral muscular dystrophy (FSHD) is both a genetic & epigenetic condition characterized by progressive muscle weakness involving facial, scapular, and humeral muscle groups early, and pelvic and peroneal muscle groups later.1,2 There are two types of FSHD (FSHD1 and FSHD2) that are clinically identical, but distinguished by their different genetic causes. Incidence and Prevalence Prevalence is estimated between 4-10 per 100,000. Approximately 95% of FSHD cases are FSHD1; the remaining cases are FSHD2.3 © 2020 eviCore healthcare. All Rights Reserved. 1 of 9 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines V1.0.2020 Symptoms Signs and symptoms can begin anytime between childhood and adulthood, but typical manifestations occur during the teenage years to early 20s in 90% of affected individuals.1,3 There is a severe infantile form of FSHD in which muscle weakness is present from birth.3 Symptoms of FSHD include: Progressive facial muscle weakness (seen by difficulty with whistling) and shoulder girdle muscle weakness and atrophy Upper arm weakness and atrophy (“Popeye arms”), often asymmetric Pelvic muscle weakness and atrophy develop later Gait weakness, foot drop, calf hypertrophy Scapular winging Exercise intolerance Pain Extra-muscular manifestations include hearing loss (common) and vision deterioration (rare) Severity ranges from almost asymptomatic weakness to severe restrictions of activities of daily living with some individuals requiring a wheel chair by 40 years of age. Cause FSHD is caused by inappropriate expression of the DUX4 gene in muscle cells. The DUX4 gene is located within a microsatellite region called D4Z4, and relaxation of the chromatin in this region is believed to cause the aberrant expression.3 In FSHD1, the chromatin relaxation is caused by a deletion or contraction of a repeated stretch of DNA (called the D4Z4 repeat). Symptoms arise when this deletion occurs in the context of a permissive nearby haplotype (called 4A). Inheritance with another haplotype results in non-penetrance of the deletion, and FSHD1 is not likely. In FSHD2, the chromatin relaxation is caused by the loss of methylation at D4Z4. This D is commonly caused by a mutation in the SMCHD1 gene.2 M Inheritance H S The pattern of inheritance differs between FSHD1 and FSHD2. F FSHD1 is inherited in an autosomal dominant pattern, with symptoms only occurring when the D4Z4 deletion occurs in the presence of the permissive haplotype. Without the presence of a specific chromosome 4A haplotype, a D4Z4 region deletion will not lead to the FSHD1 disorder. © 2020 eviCore healthcare. All Rights Reserved. 2 of 9 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines V1.0.2020 FSHD2 inheritance is digenic, with symptoms only occurring when a mutation in SMCHD1 occurs with the permissive 4A haplotype. The inheritance is not simply autosomal dominant, as SMCHD1 sorts independently from the permissive 4A haplotype locus: they are not always inherited together or from the same parent, as is the case with FSHD1. Between 10 and 30% of individuals diagnosed with FSHD have no family history. In these putative non-familial cases the genetic change occurred either de novo or the parents may be mosaic for the causative genetic change. Diagnosis Diagnosis of FSHD is suggested by clinical phenotype and inheritance pattern, and confirmed by molecular testing. Because of the complex inheritance, careful correlation between clinical presentation and molecular result is essential. Diagnostic features should include a facial, scapular, humeral, and/or peroneal distribution of weakness and atrophy. Presence of a clinical phenotype more consistent with FSHD than other myopathies is an important diagnostic consideration. Note, myotonic dystrophy type 1 and 2 are very similar to FSHD and may only be distinguished by molecular testing. Biochemical abnormalities are nonspecific but point in the direction of muscle damage. Creatine kinase (CK) is normal to elevated, but it is not typically greater than 1500 IU/L. EMG shows mild myopathic changes. Muscle biopsy is usually reserved for cases in which molecular testing is inconclusive. If a muscle biopsy is performed, results typically show nonspecific, chronic myopathic changes and dystrophy. Occasionally there can be inflammatory changes present significant enough to suggest an inflammatory myopathy. The University of Rochester's National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy defines definite FSHD diagnosis as:4 Weakness of facial muscles, and Either of the following D o Scapular weakness, or M o Foot dorsiflexor weakness, AND H Absence of eye involvement (ptosis or extraocular muscle weakness), and S F Absence of an alternative diagnosis on muscle biopsy, and EMG results that do not demonstrate myotonia or neurogenic changes 4 Probable FSHD diagnosis is defined as either: Weakness of facial muscles, or © 2020 eviCore healthcare. All Rights Reserved. 3 of 9 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines V1.0.2020 Either of the following o Scapular weakness, or o Foot dorsiflexor weakness, and Absence of eye involvement (ptosis or extraocular muscle weakness), and Absence of an alternative diagnosis on muscle biopsy, and EMG results that do not demonstrate myotonia or neurogenic change OR Weakness of facial muscles, and Either of the following o Scapular weakness, or o Foot dorsiflexor weakness, and Treatment There are no disease-modifying treatments currently available for FSHD. Management is symptom driven and primarily consists of support needed to address loss of strength. Hearing loss and rarer sequelae such as vision impairment or decreased lung function should be assessed and addressed as needed. Standard of care and management guidelines for confirmed FSDH diagnosis include:5 Evaluation by physical therapy to address functional limitations Help determining standard follow-up schedules to monitor for complications (such as pulmonary function testing and ophthalmologic screenings), and the need for assistive devices Assessments for hearing and vision loss and other orthopedic interventions Pain management to avoid compounding existing mechanical limitations. Survival D FSHD is not typically life shortening, but does lead to increased morbidity. M H S Test information F Introduction Testing for FSHD may include Southern blot analysis and gene sequencing. © 2020 eviCore healthcare. All Rights Reserved. 4 of 9 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines V1.0.2020 FSHD1 testing: Deletion assessment and Haplotyping Molecular testing for FSHD starts with assessment for the more common FSHD1. This testing consists of Southern blot analysis of the D4Z4 locus (reported as a number of D4Z4 repeats) and determination of the associated haplotype. The normal range is defined as 11-100 repeat units. The FSHD-associated repeat range is defined as 1-10; however, to be pathogenic, the contraction needs to occur in the context of the permissive 4A haplotype. Borderline repeat lengths of 10 or 11 require clinical phenotype to interpret, as they may or may not be associated with FSHD in a given individual, even in the presence of the 4A haplotype. This analysis will detect causative variants in 95% of clinically affected individuals.3 FSHD2 testing: Methylation analysis and SMCHD1 sequencing Molecular testing for FSHD2 consists of determining the methylation status of the D4Z4 region. Southern blot analysis of the D4Z4 region: methylation levels below 25% are consistent with an FSHD2 diagnosis. Again, to be pathogenic, the contraction needs to occur in the context of the permissive 4A haplotype. If methylation analysis is abnormal, SMCHD1 gene sequencing may be performed to determine the causative mutation. SMCHD1 deletion/duplication analysis will find gene rearrangements that are too large to be detected by sequencing. Large deletions in SMCHD1 are infrequently reported; therefore, deletion/duplication analysis is done as second tier testing in FSHD2. This analysis will detect causative variants in less than 5% of clinically affected individuals.3 Guidelines and evidence D Introduction M The following section includes relevant guidelines and evidence pertaining to FSHD H testing. S F American Academy of Neurology The American Academy of Neurology Evidenced-based Guideline for Clinicians (2015) 5 considers the following to be Level B practice recommendations: © 2020 eviCore healthcare. All Rights Reserved. 5 of 9 400 Buckwalter Place Boulevard, Bluffton, SC 29910
Load more

Recommended publications
  • Brachio-Cervical Inflammatory Myopathy with Associated Scleroderma Phenotype and Lupus Serology Andrew F
    Clinical/Scientific Notes Andrew F. Gao, MD BRACHIO-CERVICAL INFLAMMATORY myopathy with the distinctive prominent B-cell infil- Philip A. Saleh, MD MYOPATHY WITH ASSOCIATED SCLERODERMA trates and endomysial MAC deposition (figure). Charles D. Kassardjian, PHENOTYPE AND LUPUS SEROLOGY The patient was treated with high-dose IV meth- MD ylprednisolone for 4 days, followed by 1 mg/kg oral Ophir Vinik, MD Brachio-cervical inflammatory myopathy (BCIM) is prednisone and a gradual taper and azathioprine. David G. Munoz, MD a unique clinicopathologic entity characterized by She received monthly IV immunoglobulin. At 1 neck and upper extremity weakness with relative spar- 5-month follow-up, strength improved 4 /5 in the Neurol Neuroimmunol affected muscles. The CK level declined to 167 IU/L. Neuroinflamm ing of lower extremities and commonly associated 2018;5:e410; doi: 10.1212/ with connective tissue diseases or myasthenia gravis Dysphagia improved, and G-tube feeding could be NXI.0000000000000410 and serum autoantibodies (e.g., antinuclear antibody discontinued with resumption of solid oral diet. [ANA], anti–double stranded DNA [dsDNA], and Discussion. Our case is a prototypical example of anti–acetylcholine receptor).1 Muscle pathology is BCIM, demonstrating the clinicopathologic features distinctive, with prominent B-cell infiltrates and en- first described by Pestronk.1 They reported that the domysial membrane attack complex (MAC; C5b-9) most commonly associated conditions were myasthe- deposition. Despite the detailed original series, there nia gravis (40%) and rheumatoid arthritis (20%). have been no subsequent reports (besides abstracts2,3) Muscle biopsies showed extensive inflammatory infil- demonstrating the full clinicopathologic features of trates with at least 1 prominent CD201 B-cell focus, BCIM.
    [Show full text]
  • Dropped Head Syndrome Due to Neuromuscular Disorders: Clinical
    Neurology International 2019; volume 11:8198 Dropped head syndrome due inflammatory polyneuropathy (CIDP),11 to neuromuscular disorders: neuromuscular causes include myasthenia Correspondence: Ahmet Z. Burakgazi, gravis (MG),12-14 Lambert-Eaton myasthe- Neuroscience Section, Department of Clinical manifestation and nia syndrome (LEMS),15 muscular causes Medicine, Virginia Tech Carilion School of evaluation includes primary inflammatory such as Medicine, 3 Riverside Circle, Roanoke, VA polymyositis,16 scleromyositis,17,18 isolated 24016, USA. inflammatory axial myopathy,19 primary Tel.: +1.540-521-4592. Ahmet Z. Burakgazi, Perry K. E-mail: [email protected] Richardson, Mohammad Abu-Rub non-inflammatory such as nemaline myopa- 20-22 thy, mitochondrial myopathy, congeni- Key words: Dropped head syndrome, neuro- Virginia Tech Carilion School of 23 24 tal myopathy, FSHD, and isolated neck muscular disease. Medicine, Roanoke, VA, USA extensor myopathy (INEM).19 Contributions: the authors contributed equally. Conflict of interest: the authors declare no Abstract General approach: clinical mani- potential conflict of interest. festation and evaluation In this article, we discuss the clinical Funding: none. approach to patients with dropped head syn- DHS occurs as a result of weakness of drome and identify the various neuromus- posterior neck muscles. It usually disap- Received for publication: 11 June 2019. cular causes of dropped head syndrome pears with supine position. The common Accepted for publication: 18 June 2019. including muscle, neuromuscular junction, chief complaints are “chin on the chest” and This work is licensed under a Creative peripheral nerve and motor neuron etiolo- “difficulty maintaining a forward gaze”. It gies. We aim to increase awareness of Commons Attribution NonCommercial 4.0 may contribute to dysphagia and has cos- License (CC BY-NC 4.0).
    [Show full text]
  • Idiopathic Inflammatory Myopathy
    Idiopathic Infl ammatory Myopathy: Treatment Options Stephen J. DiMartino, MD, PhD Corresponding author ing PM or IBM can be more diffi cult [ 2 ]. The following Stephen J. DiMartino, MD, PhD noninfl ammatory myopathies and neurologic conditions Weill Medical College, Cornell University; and Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. can also present with proximal muscle weakness: cen- E-mail: [email protected] tral and peripheral nervous system disorders, adult-onset Current Rheumatology Reports 2008, 10: 321– 327 muscular dystrophies (eg, limb-girdle muscular dystro- Current Medicine Group LLC ISSN 1523-3774 phy, fascioscapulohumeral muscular dystrophy, Becker’s Copyright © 2008 by Current Medicine Group LLC muscular dystrophy), metabolic myopathies (eg, phospho- fructokinase defi ciency, acid-maltase defi ciency, carnitine palmityl-transferase II defi ciency, mitochondrial myopa- Idiopathic infl ammatory myopathy (IIM) comprises a thies), endocrine myopathies (eg, hypo- or hyperthyroidism, group of rare disorders in which there is an immune- Cushing’s syndrome, acromegaly), neuromuscular junction mediated attack on skeletal muscle, the consequence of disorders (eg, myasthenia gravis, Eaton-Lambert syndrome), which is muscle damage and weakness in the patient. viral myopathy, and toxic myopathy. As in other infl ammatory diseases, the general approach Today, statin myopathy is frequently considered in to therapy is use of immunosuppressive agents. the differential diagnosis of weakness or myalgia given Many options exist for IIM treatment, but therapeutic these agents’ high use in clinical practice [ 3 ]. Differen- approaches are based mostly on empirical evidence tiation among these entities often can be accomplished and small studies, many of which are uncontrolled.
    [Show full text]
  • A Case of Dermatomyositis with Secondary Sjögren's Syndrome
    162 A Case of Dermatomyositis with Secondary Sjögren’s Syndrome- Diagnosis with Follow-up Study of Technetium-99m Pyrophosphate Scintigraphy Ching-Tang Huang1, Ying-Chu Chen1, Chingtsai Lin2, Yu-Chun Hsiao3, Lai-Fa Sheu4, Min-Chien Tu1 Abstract Purpose: To report a case of dermatomyositis (DM) with secondary Sjögren’s syndrome (SS) and propose the clinical application of technetium-99m pyrophosphate (99mTc-PYP) scan. Case Report: A 50-year-old woman had progressive proximal muscle weakness of bilateral thighs, myalgia, tea-colored urine, and exercise intolerance for 6 months. Physical examination showed malar rash, V-sign, periungual erythema, and mechanic hands. Neurological assessment showed symmetric pelvic-girdle weakness, myopathic face, waddling gait, but preserved deep tendon reflex and sensory functions. DM was diagnosed on the basis of typical rashes and serum creatinine kinase elevation (7397 IU/L). Aside from myopathic symptoms, dry eye and mouth were reported. Thorough autoantibody searches showed positive anti-SSA/Ro antibody (198 U/ml). Both Schirmer's test and sialoscintigraphy were positive, leading secondary SS as diagnosis. Initial 99mTc-PYP scan revealed increased radiouptake in the muscles of bilateral thighs, compatible with clinical assessment. Follow- up scan three months later shows abnormal but attenuated radiouptake at bilateral thighs, in the presence of nearly-complete clinical recovery. Conclusion: DM with secondary SS in adult is a unique disease entity, with predominantly myopathic symptoms and satisfactory therapeutic response as its characteristics. Our serial muscle imaging studies suggest that 99mTc-PYP scan is at once anatomically-specific and persistently-sensitive to microstructural damages within inflammatory muscles, enabling clinician to monitor disease activity and therapeutic response.
    [Show full text]
  • Approach to Patients with Neuromuscular Disorders
    Approach to Patients With Neuromuscular Disorders Anthony A. Amato, MD Chief, Neuromuscular Division and Director, Clinical Neurophysiology Laboratory Brigham and Women’s Hospital Associate Professor of Neurology Harvard Medical School Boston, Massachusetts INTRODUCTION a true sensory level is not evident in GBS but should be present in transverse myelitis and other structural abnormalities involving the The approach to patients with neuromuscular disorders is chal- spinal cord. lenging. As in other neurological diseases the key to arriving at the correct diagnosis is careful localization of the lesion. Weakness can The presence of motor and sensory symptoms and signs are helpful be the result of central lesions (brain or spinal cord processes—e.g., in distinguishing peripheral neuropathies from anterior horn cell brainstem infarct, central pontine myelinolysis, transverse myelopa- disorders, myopathies, and neuromuscular junction disorders. thy), anterior horn cell disease (e.g., amyotrophic lateral sclerosis However, some types of peripheral neuropathy are predominantly [ALS], poliomyelitis), peripheral neuropathy (e.g., Guillain-Barré or purely motor and thus can be difficult to distinguish these other syndrome [GBS]), neuromuscular junction defects (botulism, disease processes. Most neuropathies are associated with distal Lambert-Eaton myasthenic syndrome [LEMS], myasthenia gravis greater than proximal weakness. However, significant proximal [MG]), or myopathic disorders. The most important aspect of as- weakness can be seen in certain peripheral neuropathies (e.g., GBS, sessing individuals with neuromuscular disorders is taking a thor- chronic inflammatory demyelinating polyneuropathy [CIDP]). ough history of the patient’s symptoms, disease progression, and Further, although usually associated with proximal weakness, past medical and family history as well as performing a detailed certain myopathies and rarely even neuromuscular junction disor- neurologic examination.
    [Show full text]
  • Systemic Lupus Erythematosus- Myositis Overlap
    Clinics and Practice 2011; volume 1:e89 Systemic lupus erythematosus- same patient. 1 Myositis (polymyositis PM or dermatomyositis DM) identifies a group of Correspondence: Faten Frikha, Department of myositis overlap syndrome: patients in whom the mascular weakness is Internal Medicine, Hospital of Hedi Chaker, 3029 report of 6 cases the principle clinical feature often associated Sfax, Tunisia. with muscle pain, tenderness and wasting, or E-mail: [email protected] Fatma Maazoun, 1 Faten Frikha, 1 other form of connective tissue diseases; the Key words: overlap syndrome, systemic lupus ery - Mouna Snoussi, 1 Neila Kaddour, 1 muscle biopsy generally demonstrates areas of thematosus, myositis, classification criteria, cor - Hatem Masmoudi, 2 Zouhir Bahloul 1 muscle fibre necrosis accompanied by intersti - ticosteroid. tial and/or perivascular cellular infiltrates. 1Department of Internal Medicine, Received for publication: 22 September 2011. Myositis associated with overlap syndromes is Hospital of Hedi Chaker; 2Laboratory of Accepted for publication: 12 October 2011. usually of paroxysmal variety and has been immunology, Hospital Habib Bourguiba, associated with one or another of connective This work is licensed under a Creative Commons Sfax, Tunisia tissue disorders [Systemic Sclerosis (SSc), Attribution NonCommercial 3.0 License (CC BY- Rheumatoid arthritis (RA), Sjögren’s syn - NC 3.0). drome or systemic lupus erythematous (SLE)]. ©Copyright F. Maazoun et al., 2011 Pearson and Bohan found an incidence of 21% Licensee PAGEPress, Italy Abstract 2 of this type of myositis. Myositis is a rare com - Clinics and Practice 2011; 1:e89 plication of systemic lupus erythematous 3,4 doi:10.4081/cp.2011.e89 The incidence of myositis in patients with occurring in almost 4-16% of cases of SLE 3,5,6 systemic lupus erythematosus (SLE) is low and such association is considered to be an among different series.
    [Show full text]
  • Leg Weakness in a 66-Year-Old Woman: a Common Presentation of an Uncommon Disease
    A SELF-TEST IM BOARD REVIEW JAMES K. STOLLER, MD, EDITOR ON A ANDREY S. STOJIC, MD, PhD TAREK MEKHAIL, MD BRYAN E. TSAO, MD CLINICAL Department of Neurology, Cleveland Clinic Department of Hematology and Department of Neurology, Oncology, Cleveland Clinic Cleveland Clinic CASE Leg weakness in a 66-year-old woman: A common presentation of an uncommon disease 66-YEAR-OLD WOMAN presents with pro- Blood pressure while sitting is 153/81 mm A gressive, painless weakness of the proxi- Hg, heart rate 75; blood pressure while stand- mal legs, which began 2 years ago. The onset ing is 106/71 mm Hg, heart rate 87. She is alert was gradual: at first she had difficulty standing and appropriate, and her cognition is intact. from a sitting position, such as when rising Cranial nerves II to XII are normal except for a from a chair, but over a 1-year period the weak- soft voice. She can swallow water normally. ness progressed to the point where she could no She has no ptosis. longer stand or walk without assistance. Arm Motor examination shows normal tone strength is not impaired. Six months before her and muscle bulk throughout. There is no visit she developed numbness and tingling in pain to palpation over the spine. Strength in the legs to the mid-calf level. her neck flexors and extensors is graded 4 on Review of systems reveals she has unin- the 5-point Medical Research Council scale. She has: tentionally lost 50 pounds over the past 2 She has normal strength in her arms; both •Leg years.
    [Show full text]
  • Inflammatory Myopathies
    South African Rheumatism & Arthritis Association Inflammatory myopathies Myopathy is a general medical term used to describe a number of conditions affecting the muscles. All myopathies cause muscle weakness. The idiopathic inflammatory myopathies are a group of diseases in which inflammation occurs in muscles and often in organs and tissues other than muscle. muscle weakness, and, in some cases, muscle pain. They include • Dermatomyositis • Polymyositis • Juvenile dermatomyositis • Juvenile polymyositis • Myositis that occurs with other systemic (body-wide) rheumatic diseases, such as mixed connective tissue disease, lupus, and scleroderma • Autoimmune necrotizing myopathy Some muscle diseases occur when the body’s immune system attacks muscles. The result is misdirected inflammation, hence the name inflammatory myopathies. People with inflammatory myopathies may have these features: • Proximal weakness in the large muscles around the neck, shoulders and hips • Trouble climbing stairs, getting up from a seat, or reaching for objects overhead • Little, if any, pain in the muscles • Choking while eating or aspiration (intake) of food into the lungs • Shortness of breath and cough Sometimes patients can have the rash with no sign of muscle disease. Doctors call this form of the disease amyopathic dermatomyositis. People with dermatomyositis may also have lung inflammation that causes cough and shortness of breath. Children with the disease may have an inflammation of the blood vessels (vasculitis) that can result in skin lesions. Skin changes — People with dermatomyositis often develop a rash or other change in the skin. SARAA Patient Education Resources; by Dr Mpoti Seboka updated May 2020 1 Sout Arican Reuatis Artritis Association • Gottron’s sign or Gottron’s papules – Gottron’s sign is a flat red rash over the back of the fingers, elbows or knees.
    [Show full text]
  • Myopathology of Non-Infectious Inflammatory Myopathies – The
    ARTICLE IN PRESS Pathology – Research and Practice 204 (2008) 609–623 www.elsevier.de/prp DIAGNOSTIC SEMINAR Myopathology of non-infectious inflammatory myopathies – The current status Ekkehard Hewera,Ã, Hans H. Goebela,b aInstitute of Neuropathology, University Hospital Zurich, Zurich, Switzerland bDepartment of Neuropathology, Johannes Gutenberg University, Mainz, Germany Received 18 November 2007; accepted 4 March 2008 Abstract Besides the classical inflammatory myopathies (IM), dermatomyositis (DM), polymyositis, and inclusion body myositis, the much larger spectrum of IM includes focal and nodular myositis, granulomatous myositis, macrophagic myofasciitis, graft vs. host myositis, eosinophilic myositis, and other immune-associated conditions, some of them only recently described. In addition, paraneoplastic, statin-induced and critical illness myopathies have been considered immune-associated IM. Infectious, i.e., bacterial, viral, and parasitic IM are much less frequent in the northern hemisphere. In IM, muscle biopsy is an essential diagnostic procedure to initiate therapy. The myopathological spectrum encompasses disease-specific histopathological features, such as perifascicular atrophy in DM, non- necrotizing granulomas in sarcoid myopathy, autophagic vacuoles with tubulofilamentous inclusions in inclusion body myositis, rarely electron microscopic criteria, such as undulating tubules in endothelial cells of DM specimens, and, foremost, immunohistochemical findings. These latter features concern inflammatory infiltrates, the muscle parenchyma, the interstitial compartment, and the vasculature with varying involvement of each component in the different IM. Differences in immunohistochemical parameters among the IM, such as major histocompatibility complexes I and II, cytokines, cell adhesion molecules, different types of inflammatory cells, metalloproteinases, and complement factors procure a large gamut of data, the individual patterns of which characterize the myopathology of individual IM.
    [Show full text]
  • Systemic Sclerosis-Related Myopathy
    Vol. 2, No. 3, July 2017, 85-89 Webpage: http://rheumres.org Email: [email protected] ISSN: 2476-5856 doi: 10.22631/rr.2017.69997.1023 2017, Iranian Rheumatology Association Review Article Open Access Systemic sclerosis-related myopathy Ali Javinani1 and Hoda Kavosi2* 1Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2Assistant Professor of Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Systemic sclerosis (SSc) is an autoimmune disorder which can affect nearly every body organ. Muscle involvement is one of the most serious manifestations of SSc. It can present itself in a wide range of pathologies. It can be as indolent as a subclinical myopathy which manifests simply as a mild muscle enzyme level elevation, or it can present itself in a similar manner to other SSc organ involvements in the form of fibrosing myopathy without any existing evidence of inflammation. It can also present itself aggressively as an idiopathic inflammatory myopathy, the overlap syndrome of SSc-myositis. Due to the wide range of witnessed pathologies and the different diagnostic criteria that are used, opinions vary on the estimated prevalence of myopathy in SSc with estimates ranging from 3.3% to 14%. The severity and distribution of clinical manifestations differ among SSc-myopathy and SSc patients. These manifestations have different effects on the survival rates of patients, which will be discussed in this review. This paper will also focus on the existing treatment methods for SSc patients suffering from myopathy and their challenges. Keywords: fibrosing myopathy, idiopathic inflammatory myopathy, muscle histopathology, systemic sclerosis. Introduction __________________________ documented case of SSc-IIM in 1969.
    [Show full text]
  • Polymyositis with Mitochondrial Pathology Or Atypical Form of Sporadic Inclusion Body Myositis: Case Series and Review of the Literature
    Rheumatology International (2019) 39:1459–1466 Rheumatology https://doi.org/10.1007/s00296-019-04314-8 INTERNATIONAL CASES WITH A MESSAGE Polymyositis with mitochondrial pathology or atypical form of sporadic inclusion body myositis: case series and review of the literature George K. Papadimas1 · Charalampos Kokkinis2 · Sophia Xirou1 · Margarita Chrysanthou1 · Evangelia Kararizou1 · Constantinos Papadopoulos1 Received: 11 December 2018 / Accepted: 26 April 2019 / Published online: 4 May 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Polymyositis with mitochondrial pathology (PM-Mito) is a rare form of idiopathic infammatory myopathy with no defnite diagnostic criteria and similarities to both PM and sporadic inclusion body myositis (s-IBM). The aim of this study is to address the dilemma of whether PM-Mito is a subtype of infammatory myopathy or represents a disease falling into the spectrum of s-IBM. Herein, we report four female patients diagnosed with PM-Mito, highlighting their rather atypical clini- cal and histopathological characteristics that seem to indicate a diagnosis away from s-IBM. Muscle weakness was rather proximal and symmetrical and lacked the selective pattern observed in s-IBM. Patients had large-scale deletions in mtDNA, refecting the mitochondrial component in the pathology of the disease. Conclusively, our study adds to the limited data in the literature on whether PM-Mito is a distinct form of myositis or represents a prodromal stage of s-IBM. Although the lat- ter seems to be supported by a substantial body of evidence, there are, however, important diferences, such as the diferent patterns of muscle weakness, and the good response to treatment observed in some patients.
    [Show full text]
  • Idiopathic Inflammatory Myopathies – a Guide to Subtypes, Diagnostic
    REVIEW Clinical Medicine 2017 Vol 17, No 4: 322–8 Idiopathic inflammatory myopathies – a guide to subtypes, diagnostic approach and treatment A u t h o r s : A l e x a n d e r O l d r o y d , A J a m e s L i l l e k e r B a n d H e c t o r C h i n o y C The idiopathic infl ammatory myopathies are a group of condi- E p i d e m i o l o g y tions characterised by infl ammation of muscles (myositis) and other body systems. The diagnosis can be challenging because The IIMs are relatively rare conditions with an overall reported incidence of 11/million person-years (10 for men and 13 for of the many potential clinical features and extra-muscular 3 manifestations, which may be seemingly unrelated. An accu- women) and a prevalence of 14/100,000. ABSTRACT rate diagnosis requires up-to-date understanding of the clini- The peak age range of IIM onset is 45–60 years for adults and cal manifestations, different clinical subtypes and appropriate 5–15 years for children. Apart from inclusion body myositis (IBM), all IIM subtypes occur more commonly in women interpretation of investigations, including newly described 4 serological subtypes. This review will detail the approach to (ratio 2:1); IBM occurs twice as commonly in men as women. the diagnosis of an idiopathic infl ammatory myopathy, based on up-to-date knowledge. The recently updated classifi cation S u b t y p e s criteria and treatment options will also be described.
    [Show full text]